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iatryOnline | American Journal of Psychiatry | Psychiatric Disorders in Preschool Offspring of Parents With Bipolar Disorder: The Pittsburgh Bipolar Offspring Study (BIOS)

/ajp.psychiatryonline.org/article.aspx?articleid=102144[11/26/2011 4:46:51 PM]

The American Journal of Psychiatry, VOL. 167, No. 3

ARTICLE | January 15, 2010

Psych ia t r i c Disorders in Preschoo l Of fspr in g o f Parent s Wi t h

B ipo la r D i so rde r : The P i t t sbu rgh B ipo la r O f f sp r i ng Study

( B I OS)

Boris Birmaher, M.D.; David Axelson, M .D.; Benjamin Goldstein, M .D.; Kelly Monk , R.N.; Catherine

Kalas, R.N.; Mihaela Obreja, M.S.; Mary Beth Hickey, B.A.; Satish Iyengar, P h.D.; David Brent,

M.D.; Wael Shamseddeen, M.D.; Rasim Diler, M.D.; David Kupfer, M.D.

Am J Psychiatry 2010;167:321-330. 10.1176/appi.ajp.2009.09070977

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Copyright American Psychiatric Association

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AbstractObjective

The authors evaluated lifetime prevalence and specificity of DSM-IV psychiatric disorders and severity ofdepressive and manic symptoms at intake in preschool offspring of parents with bipolar I and II disorders.

Method

A total of 121 offspring ages 25 years from 83 parents with bipolar disorder and 102 offspring of 65

demographically matched comparison parents (29 with non-bipolar psychiatric disorders and 36 without any

ifetime psychopathology) were recruited for the study. Parents with bipolar disorder were recruited through

advertisements and adult outpatient clinics, and comparison parents were ascertained at random from the

community. Participants were evaluated with standardized instruments. All staff were blind to parental

diagnoses.

Results

After adjustment for within-family correlations and both biological parents' non-bipolar psychopathology,

offspring of parents with bipolar disorder, particularly those older than age 4, showed an eightfold greater

ifetime prevalence of attention deficit hyperactivity disorder (ADHD) and significantly higher rates of having

two or more psychiatric disorders compared to the offspring of the comparison parents. While only three

offspring of parents with bipolar disorder had mood disorders, offspring of parents with bipolar disorder,

especially those with ADHD and oppositional defiant disorder, had significantly more severe current manicand depressive symptoms than comparison offspring.

Conclusions

Preschool offspring of parents with bipolar disorder have an elevated risk for ADHD and have greater levels of

subthreshold manic and depressive symptoms than children of comparison parents. Longitudinal follow-up is

warranted to evaluate whether these children are at high risk for developing mood and other psychiatric

disorders.

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Abstract | Method | Results | Discussion | Acknowledgments | References

The study of the early manifestations of bipolar disorder in youths, particularly during early childhood, is of

prime importance because of the severe impact that this condition has on the normal psychosocial

development of children, on their families, and on society in general (13).

The single largest risk factor for the development of bipolar disorder is a positive family history of the

disorder (3). Therefore, one way to try to identify the prodromal and earliest clinical manifestations of

bipolar disorder is to study the offspring of adults with the disorder. This information is critical for developing

early interventions that may prevent the onset of pediatric bipolar disorder and promote the normal

psychosocial development of the child (3, 4).

Risk studies of pediatric bipolar disorder have shown that offspring ages 6 to 18 years of parents with bipolar

disorder have an elevated risk of developing early-onset bipolar disorder and other psychiatric disorders ( 3,

511). The largest of these studies is the Pittsburgh Bipolar Offspring Study (BIOS) (5). The BIOS showed

that school-age offspring of parents with bipolar disorder had significantly higher rates of any axis I disorder,

bipolar spectrum disorders (mostly not otherwise specified), major depressive disorder, anxiety disorders,

disruptive behavior disorders, and attention deficit hyperactivity disorder (ADHD) than offspring of communitycomparison parents. However, after adjustment for both biological parents' non-bipolar psychopathology, the

differences in the rates of major depressive disorder, disruptive behavior disorders, and ADHD were no longer

significant.

The above-noted studies were conducted with offspring age 6 and older. However, parents with either a

personal or a family history of bipolar disorder often wonder whether their preschool child's behavioral and

emotional problems are due to a bipolar diathesis, since some of these problems are reminiscent of their own

or their relatives' problems during childhood. The few studies of preschool offspring of parents with bipolar

disorder suggest that relative to offspring of comparison parents (mostly healthy), these children have higher

rates of observed behavioral disinhibition, disruptive and depressive symptoms, fidgetiness, hyperactivity,

disproportionate levels of aggression, and difficulty managing anger and hostile impulses during observed

nteractions with peers and unknown adults (1216). Some of these problems (disruptive and depressive

symptoms) were found to persist and even increase (e.g., depression) over time (14). However, further

research is needed to confirm these findings since these studies used very small samples of children and

parents with bipolar disorder and had other methodological limitations, as delineated elsewhere ( 5, 7).

Epidemiological and clinical studies have shown that clinically relevant symptoms and psychiatric disordersare reliably diagnosed in preschool children as young as 2 years old (1720). Symptoms of major depressive

disorder are also reliably ascertained in this population and are associated with significant psychosocial

mpairment and high rates of mood disorders in family members (18, 19, 21, 22). Although several case

reports (2327) and a recent study (24) showed that preschoolers can be diagnosed with DSM-IV bipolar

disorder, the diagnosis of mania in young children remains controversial, and further longitudinal research is

warranted.

Our primary goal in this study was to evaluate whether preschool offspring of parents with bipolar disorder

had significantly more lifetime DSM-IV axis I disorders than a demographically matched sample of preschool

offspring of community parents (with and without non-bipolar psychopathology). In addition to categorical

diagnoses, since subthreshold mood symptoms may precede the onset of full-blown mood disorders, the

presence and severity of mood symptoms at intake were explored. Based on the available literature, we

hypothesized that offspring of parents with bipolar disorder would have higher rates of ADHD, disruptive

behavior disorders, and anxiety and mood disorders and higher ratings on depressive and manic symptom

scales relative to offspring of comparison parents.

Method

Participants

Parents (probands)

As part of BIOS, parents with DSM-IV bipolar I or bipolar II disorder who had preschool children were

recruited through advertisements (60%), adult bipolar studies (9%), and adult outpatient clinics (31%).

There were no differences between recruitment sources in bipolar subtype, age at onset of bipolar disorder

(17.35 years [SD=6.2]), or rates of non-bipolar disorders. Exclusion criteria included current or lifetime

diagnoses of schizophrenia, mental retardation, and mood disorders secondary to substance abuse, medical

conditions, or medications.

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TREATING BIPOLAR DISORDERA Quick

Reference Guide

Guideline Watch: Practice Guideline for

the Treatment of Patients With Bipolar

Disorder, 2nd Edition

Parenting an adult child w ith bipolar

disorder in later life.

The Journal of nervous and mental disease

2009 May

Paternal psychiatric disorders and

children's psychosocial development.

Lancet 2009 Aug 22
http://psychnews.psychiatryonline.org/PNhome.aspx?journalID=61&pageid=1http://psychiatryonline.org/content.aspx?bookid=3&sectionid=1349862#314214%22http://psychiatryonline.org/content.aspx?bookid=4&sectionid=1333497#250000%22http://ajp.psychiatryonline.org/collection.aspx?categoryid=5083http://ajp.psychiatryonline.org/collection.aspx?categoryid=5123http://ajp.psychiatryonline.org/collection.aspx?categoryid=5124http://psychnews.psychiatryonline.org/newsarticle.aspx?articleid=179950&RelatedNewsArticles=truehttp://psychnews.psychiatryonline.org/newsarticle.aspx?articleid=179950&RelatedNewsArticles=truehttp://psychnews.psychiatryonline.org/newsarticle.aspx?articleid=179986&RelatedNewsArticles=truehttp://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1663219#110108http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1663219#110108http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1682557#148430http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1682557#148430http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1682557#148430http://www.ncbi.nlm.nih.gov/pubmed/19440101http://www.ncbi.nlm.nih.gov/pubmed/19440101http://www.ncbi.nlm.nih.gov/pubmed/19411102http://www.ncbi.nlm.nih.gov/pubmed/19411102http://www.ncbi.nlm.nih.gov/pubmed/19411102http://www.ncbi.nlm.nih.gov/pubmed/19411102http://www.ncbi.nlm.nih.gov/pubmed/19440101http://www.ncbi.nlm.nih.gov/pubmed/19440101http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1682557#148430http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1682557#148430http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1682557#148430http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1663219#110108http://ajp.psychiatryonline.org/content.aspx?bookid=28&sectionid=1663219#110108http://psychnews.psychiatryonline.org/newsarticle.aspx?articleid=179986&RelatedNewsArticles=truehttp://psychnews.psychiatryonline.org/newsarticle.aspx?articleid=179950&RelatedNewsArticles=truehttp://psychnews.psychiatryonline.org/newsarticle.aspx?articleid=179950&RelatedNewsArticles=truehttp://ajp.psychiatryonline.org/collection.aspx?categoryid=5124http://ajp.psychiatryonline.org/collection.aspx?categoryid=5123http://ajp.psychiatryonline.org/collection.aspx?categoryid=5083http://psychiatryonline.org/content.aspx?bookid=4&sectionid=1333497#250000%22http://psychiatryonline.org/content.aspx?bookid=3&sectionid=1349862#314214%22http://www.ncbi.nlm.nih.gov/pubmedhttp://psychnews.psychiatryonline.org/PNhome.aspx?journalID=61&pageid=1


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Comparison parents, group-matched by age, sex, and neighborhood (based on the postal codes and area

codes and the first three digits of telephone numbers of the parents with bipolar disorder), were recruited

from the community via telephone using random dialing by the University Center for Social and Urban

Research of the University of Pittsburgh. The exclusion criteria for the comparison parents were the same as

those for the parents with bipolar disorder, with the additional requirements that neither of the biological

parents could have bipolar disorder and they could not have a first-degree relative with bipolar disorder.

However, they could have other psychiatric disorders or be healthy.

Offspring of bipolar and comparison parents

Except for children with a condition that impeded their participation in the study (e.g., mental retardation),

all offspring ages 25 from each family were included.

Procedures

The study was approved by the University of Pittsburgh Institutional Review Board. Informed consent was

obtained from all parents.

For all parents who participated as probands and 46% (68/148) of the biological co-parents, psychiatric

disorders were ascertained face-to-face using the Structured Clinical Interview for DSM-IV (SCID). Lifetime

ADHD, disruptive behavior disorders, and separation anxiety disorder were ascertained using the respective

tems from DSM-IV. The SCID kappa values were 0.8.

The Family HistoryResearch Diagnostic Criteria method ( 28) (plus ADHD, separation anxiety disorder, and

disruptive behavior disorder items from the Schedule for Affective Disorders and Schizophrenia for School-

Age ChildrenPresent and Lifetime Version [K-SADS-PL]) (29) was used to ascertain psychiatric history from

biological co-parents who were not seen in face-to-face interviews, as well as for siblings and second-degree

relatives.

Parents were interviewed about their children for the presence of lifetime psychiatric disorders using the K-

SADS-PL. In addition, the severity of the worst past and current (a month preceding the interview) manic orhypomanic and depressive symptoms were assessed using the Kiddie Mania Rating Scale (30, 31) and the

depression section of K-SADSPresent Episode Version (32) (for these instruments, see

www.wpic.pitt.edu/research under "Assessment Instruments"). Individual symptom items are rated on 5- or

6-point Likert scales (ranging from "not present" to "severe" or "extreme"). The sums of 13 manic symptom

tems on the Kiddie Mania Rating Scale (range=064; for the scoring instructions, see reference 30), the five

manic items that do not overlap with ADHD symptoms and that were shown to separate preschool children

with bipolar disorder from children with and without non-bipolar psychopathology (range=025) (24), and 12

depression items from the K-SADS depression section that correspond to the DSM-IV symptoms of major

depressive disorder (range=060) (32) were analyzed. Pervasive developmental disorders were ascertained

using a DSM-IV symptom checklist (Cronbach alpha=0.9).

The K-SADS-PL has adequate psychometric properties for evaluating psychiatric disorders in preschool

children (8, 3335). Details regarding the procedures to use the K-SADS-PL in preschoolers and its

psychometric properties and limitations as compared with other instruments for preschool children have been

described in detail elsewhere (35). Briefly, the K-SADS-PL was administered by experienced bachelor's- or

master's-level interviewers who were instructed on how to ask parents developmentally appropriate questionsregarding their children's psychopathology. For example, a normal child is expected to be elated in certain

situations and express exaggerated concepts about his or her abilities, which should not be misinterpreted as

pathological elation or grandiose ideations (24). Mood symptoms that are common in other psychiatric

disorders (e.g., irritability, agitation) were not rated as present in the mood sections unless they intensified

with the onset of abnormal mood. Comorbid diagnoses were not assigned if they occurred exclusively during

a mood episode. Results of the interview were always presented to child psychiatrists, who were ultimately

responsible for all diagnoses. Only children with clinically relevant and persistent symptoms that affected

their psychosocial functioning were diagnosed as having a psychiatric disorder.

All diagnoses were made using DSM-IV criteria. However, operationalized criteria for bipolar disorder not

otherwise specified were used (36). In children and adolescents with this subtype of bipolar disorder, the

clinical picture, comorbid disorders, family history, and longitudinal outcome have been shown to be similar

to but less severe than in youths with bipolar I disorder (36). Moreover, approximately 40% of youths with

bipolar disorder not otherwise specified, especially those with a family history of bipolar disorder, converted

to bipolar I or II disorder (37). With the exception of bipolar disorder, major depressive disorder, and

pervasive developmental disorders in children and bipolar disorder not otherwise specified in biological co-

parents, no other not-otherwise-specified disorders were included in this analysis. As described in further

detail elsewhere, kappa values for all disorders ranged from 0.80 to 0.90 (35).

Caregiver-Teacher Report Forms (38) were requested from all caregivers of children who were attending day

care or preschool programs.

Approximately 75% of the assessments were carried out in the participants' homes. To ensure blindness to

parental diagnoses, different interviewers assessed the parents' and children's psychopathology, and the child

psychiatrists were blind to parental diagnoses. Interviewers were asked to complete a "guess form" reporting

whether they thought the parents were in the bipolar disorder group or the comparison group. They guessed

correctly in 74% of the cases. Of those who guessed correctly, 59% were "not at all certain" and 33% were

"somewhat certain" about their guess. In addition, in 8% of the cases they were "definitely certain" or the

blind was broken by the parent. The psychiatrists remained blind to parental status in all cases. All parents',

children's, and relatives' diagnoses were made according to the best-estimate procedure (39). Socioeconomic

status was ascertained using the Hollingshead scale (40).


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Statistical Analyses

The differences in demographic and clinical characteristics between the groups were evaluated by t test, chi-

square test, and Fisher's exact test, as appropriate. Since both biological parents' non-bipolar

psychopathology may affect the risk for psychiatric disorders in their offspring and more than one child from

each family was included ("within-family correlations"), the effects of these variables were analyzed using

mixed logistic and mixed-effects nominal logistic regressions, respectively.

Effect sizes for continuous and categorical variables were calculated as described by Cohen (41). All p values

are based on two-tailed tests.

Results

Parents

The recruitment flow of parents with bipolar disorder and comparison parents has been described in detail

elsewhere (5) and is summarized in Figure 1. Since the initial screening was done over the telephone and

before participants' consent was obtained, the institutional review board did not permit the recording of

demographic information. Thus, comparisons between screened individuals who declined to participate and

those who agreed to participate further are not available.

Figure 1. Recruitment Flow of Parents With Bipolar Disorder and

Community Comparison Parents

Eighty-three parents (67 of them [80.7%] female) with bipolar disorder (51 with bipolar I disorder and 32

with bipolar II disorder) and 65 community comparison parents (29 with non-bipolar psychiatric disorders

and 36 without any psychopathology) who had offspring 25 years old were recruited to the study. In only

two families did both parents have bipolar disorder. About 80% of parents with bipolar disorder reported that

their initial DSM mood episode started when they were 22 years old and 30% before they were 13 years

old.

The comparison parents had no first- or second-degree family history of bipolar disorder.

Demographic comparisons

Except for a greater likelihood of being female among parents with bipolar disorder than among comparison

parents, there were no between-group differences in demographic characteristics (Table 1). On average, both

groups of parents included two children in the study.

Table 1. Demographic Characteristics and Lifetime Axis I Psychiatric Disorders of Proband Parents

With Bipolar Disorder and Community Comparison Proband Parents
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Axis I disorders in probands

With the exception of similar prevalences of separation anxiety disorder, dysthymic disorder, and binge

eating disorder, all other psychiatric disorders were present at higher rates in the parents with bipolar

disorder than in the comparison parents (p values, 0.04; effect sizes, 0.311.68). Within the bipolar parent

group, there were no significant differences in the rates of psychopathology between those recruited through

advertisement and those recruited by other means.

Axis I disorders in the biological co-parents

There was no significant difference between parents with bipolar disorder and comparison parents in the

proportion of direct assessments used to ascertain the nonproband biological parent's psychiatric disorders(56% and 44%, respectively). The biological co-parents of offspring of parents with bipolar disorder had

higher rates of any axis I disorder than the biological co-parents of offspring of comparison parents (40.9%

compared with 24.7%, p=0.02). They also had higher rates of bipolar disorder (3.2% compared with 0%),

substance abuse (26% compared with 16%), and disruptive behavior disorders (3.2% compared with 1.2%),

but these differences did not reach statistical significance.

Offspring

Demographic comparisons

A total of 121 offspring of parents with bipolar disorder and 102 offspring of comparison parents (58 from

parents with at least one parent with non-bipolar psychopathology and 44 from healthy parents) were

recruited. There were no between-group differences in demographic characteristics (Table 2). As expected,

the mother was the reporter for most (78.9%) children. At intake, five children of the parents with bipolar

disorder were taking psychotropic medications, mainly stimulants. None of the children of the comparison

parents were taking medications.

Table 2. Demographic and Clinical Characteristics of Offspring of Bipolar Parents and Offspring of

Community Comparison Parents

Axis I disorders

As shown in Table 2, relative to the offspring of comparison parents, the offspring of parents with bipolar

disorder showed significantly greater lifetime prevalence of any axis I disorder, disruptive behavior disorders,

ADHD, and two or more disorders (p values, 0.05; effect sizes, 0.240.48); they also had a higher rate of

oppositional defiant disorder, although this difference did not reach statistical significance. Two offspring of

parents with bipolar disorder had bipolar disorder not otherwise specified (they did not meet the DSM-IV

duration criteria for bipolar disorder), one had depressive disorder not otherwise specified, and one had

adjustment disorder with depressed mood. The offspring of comparison parents did not have mood disorders.

Except for oppositional defiant disorder, which was diagnosed equally in children younger and older than age

4, about 80% of disorders occurred in children older than age 4.

There were no differences in rates of psychiatric disorders between offspring of parents with bipolar I disorder

and offspring of parents with bipolar II disorder. Parental age at onset of mood disorder was not significantly

associated with offsprings' rate of having any axis I disorder. Among offspring of parents with bipolar

disorder, having any axis I disorder was not significantly associated with the mothers' lifetime bipolar

diagnosis or any active axis I disorder at the time of assessment.

There were no differences in rates of psychiatric disorders between offspring of parents whom the

nterviewers correctly guessed had bipolar disorder and those of parents whom the interviewers incorrectly

guessed had bipolar disorder. The same results were observed among offspring of parents with bipolar

disorder.

Mixed-effects logistic regressions

Adjusting for both biological parents' non-bipolar psychopathology and within-family correlations showed that
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relative to offspring of comparison parents, offspring of parents with bipolar disorder had a significantly

higher risk for ADHD (odds ratio=8.17, 95% CI=1.352.6) and for having two or more disorders (odds

ratio=6.4, 95% CI=1.140). Comparisons for disruptive behavior disorders and any axis I disorder were not

significant.

Severity of manic and depressive symptoms

As depicted in Table 3, scores for the Kiddie Mania Rating Scale (5 and 13 items) and the 12-item K-SADS

depression section were significantly higher in offspring of the parents with bipolar disorder relative to those

of offspring of comparison parents. Adjusting for age, sex, parental diagnoses, and child's oppositional

defiant disorder and ADHD did not change the results. However, there were significant interactions, with

offspring with ADHD or oppositional defiant disorder and a parent with bipolar disorder showing higher

scores on the Kiddie Mania Rating Scale (5 and 13 items) and K-SADS depression section (p values,


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groups were the mothers. Moreover, in about half of the cases, the psychopathology in the biological co-

parents was ascertained by interviewing the main informant. However, there were no differences between the

bipolar and comparison parent groups in the rate of mothers serving as main informants and in the

proportion of direct and indirect interviews of biological co-parents. Second, the children's psychopathology

was ascertained through parents, and parental psychiatric illnesses could have inflated the rates of reported

psychopathology in offspring. However, although the literature regarding this issue is controversial, it appears

that if there is any effect, it is small (4244). Similar biases existed for both parent groups because about

50% of the comparison parents had axis I disorders, and rates of psychiatric disorders in the offspring of

parents with bipolar disorder were not associated with their mothers' lifetime diagnosis of bipolar disorder

and acute mood symptoms at intake. In contrast to the above arguments, there were no differences in

caregiver scores between offspring of parents with bipolar disorder and offspring of comparison parents.

Nevertheless, only a few offspring who had caregiver reports had ADHD and/or oppositional defiant disorder,

and the rest of the sample was healthy. To help clarify these issues, more confirmatory work is needed using

parent reports in tandem with measures less likely to be influenced by bias (direct observation

measurements in particular). Third, the nature of the study could have attracted parents with more severe

disorders. Nevertheless, the rates of psychiatric disorders in the parents with bipolar disorder were similar to

those reported in the adult bipolar literature (45, 46). Also, even though BIOS is not an epidemiological

study, the lifetime prevalence of psychiatric disorders observed in the comparison parent group was similar

to that reported in a recent large epidemiological study in the United States (47). Fourth, no direct

observations of the preschoolers were available. Finally, although behavioral and mood disorders are

dentifiable in preschoolers, more research is needed on the way these disorders, particularly mania, manifest

n preschoolers and on what would be the most appropriate methods and instruments to assess these

conditions in this population.

Both biological parents of offspring of parents with bipolar disorder had higher rates of psychopathology than

comparison parents, and thus it is not surprising that their offspring also had significantly more

psychopathology. In fact, after taking into account both biological parents' psychopathology, between-group

differences in having any axis I disorder and disruptive behavior disorders were no longer significant.

However, rates of ADHD remained significantly higher in offspring of parents with bipolar disorder. Studies of

preschool offspring of parents with bipolar disorder that evaluated dimensional symptoms rather thancategorical disorders have also shown that these children have symptoms frequently observed in children

with ADHD, such as behavioral disinhibition, hyperactivity, and difficulty managing anger and hostile impulses

(15, 17, 19).

It is not yet clear why the results of the BIOS preschool-age study contrast with those of the BIOS and other

school-age high-risk studies (i.e., high prevalence of mood and anxiety disorders) (14, 4850). It is possible

that the K-SADS-PL was not sensitive enough to detect mood and anxiety disorders in preschoolers.

However, rates of disorders ascertained through the K-SADS-PL are similar to those found in epidemiological

studies (19, 35), and one epidemiological study using an unmodified K-SADS-PL (51) diagnosed mood and

anxiety disorders in preschoolers at rates similar to the Preschool Age Psychiatric Assessment (19). It is also

probable that in comparison with older children, nonspecific symptoms such as irritability, hyperactivity,

nattention, and impulsivity are ubiquitous manifestations of externalizing as well as internalizing

psychopathology in preschool children (9, 14, 5255). In contrast, because of the emotional and cognitive

developmental level in this population, more specific manic symptoms, such as grandiosity and elation, or

depressive symptoms, such as hopelessness and severe melancholia, may not yet be evident, and if they are

present, they are more difficult to ascertain (24). Thus, in BIOS, although these nonspecific externalizingsymptoms may indeed be accounted for by early-childhood ADHD, it is also possible that they are prodromal

or subthreshold symptoms of mood disorders, especially when accompanied by mood symptoms and a family

history of mood disorders (8, 9, 14, 16, 53, 5659). In fact, in BIOS, preschool children in the bipolar

parent group with externalizing disorders had significantly more manic and depressive symptoms than

offspring in the bipolar parent group without these disorders and offspring in the comparison parent group.

As reported in the literature, these children are at high risk for developing mood disorders ( 6064).

Only three offspring of parents with bipolar disorder had subthreshold mood disorders. However, these

children have not reached the age of highest risk for developing bipolar and major depressive disorders, and

t has been consistently shown that the rate of these disorders is likely to increase with age (5, 8, 9, 65,

66). Despite the above findings, offspring of parents with bipolar disorder, and especially offspring with

externalizing disorders, had significantly more severe manic (including elation) and depressive symptoms

than offspring of comparison parents. However, it is important to note that, in general, the severity of

ndividual manic symptoms was subclinical. Furthermore, additional research is needed to define the

boundaries between bipolar symptoms (e.g., elation, grandiosity, irritability, and mood episodicity) and the

expected broad mood fluctuations and normal fantasies about special powers and abilities and appropriately

ncreased self-concept commonly observed in preschool children (24, 67).

Because BIOS is prospectively following all children, we will be able to address these developmental issues

and delineate the types and severity of symptoms that predict subsequent conversion to bipolar disorder.

Also, because approximately 70% of the offspring of parents with bipolar disorder in our sample did not have

any diagnosable psychiatric illness and very few had subthreshold mood disorders, there is a window of

opportunity for primary prevention in this high-risk population. Thus, psychosocial interventions aimed at

helping preschool children regulate their mood, which have been found to be efficacious in preschoolers with

disruptive behavior disorders and in older children with subthreshold mood disorders, and effective treatment

of parental psychopathology may diminish the severity of, and perhaps delay or prevent the new onset of,

psychopathology in preschool offspring of parents with bipolar disorder (4, 24, 6871).

Acknowledgments


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The authors thank Carol Kostek and Mary Kay Gill, M.S.N., for their assistance with manuscript preparation,

the University Center for Social and Urban Research staff, the Pittsburgh Bipolar Offspring Study interviewers

(Ryan Brown, Nick Curcio, Ronna Currie, Gail Oterson, Elizabeth Picard, and Lindsay Virgin), Scott Turkin,

M.D., and the Dubois Regional Medical Center Behavioral Health Services staff for their collaboration. The

authors also thank Drs. Shelli Avenevoli and Editha Nottelmann from NIMH for their support.

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Copyright American Psychiatric Association. All rights reserved.Print ISSN 0002-953X | Online ISSN 1535-7228

Parental Dysfunction on Children. Edited by McMahon RJ; Peters RD. New York, Kluwer

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Chang K; Howe M; Gallelli K; Miklowitz D: Prevention of pediatric bipolar disorder:

integration of neurobiological and psychosocial processes. Ann NY Acad Sci 2006; 1094:235


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